The goal of our study is to identify and to solve immunologic problems which exist in an application of fetal pancreas transplants for the treatment of Diabetes Mellitus. Thus, we hope to transplant fetal pancreases into patients under the most desirable and safe condition. The study will continue to be carried out in the genetically defined rat model followed by an initition of the next phase of our investigation in selectively bred miniature swine, as an intermediate mammal between rats and men (animals will be provided by Dr. D. Sacks, NIH). These animals are homozygous at MHC. The study will involve the following three projects: 1. Studies on specific immunotherapy in rats. To achieve prolonged survivals of allografts across RT1 barrier from the current level of 50-70 days to longer than 150 days in more than 80% of recipients by the induction of specific unresponsiveness with the treatment using donor antigen pretreatment and a short term administration of procarbazine hydrochloride and ALS. To evaluate the combination treatment of irradiation and syngeneic bone marrow transplants for induction of specific unresponsiveness to fetal pancreas allografts. To analyze the induced unresponsive state and the immune capacity of recipients. To monitor tumor susceptibility vs. resistance in pancreas recipients. II. Studies on the effects of the host's pre-existing immune state, with respect to either insulin or islet elements, on the fate of fetal pancreas iso- and allografts in rats. III. Studies on miniature swine fetal pancreases. To develop and evaluate assay procedures for fetal tissue typing. To determine the optimum fetal age for pancreas transplants. To develop a cryopreservation technique for fetal pancreases. To store tissue-typed fetal pancreases by the developed cryopreservation technique.